This invention relates in general to biological, biochemical and chemical assays, and more particularly, to a sampling and filtration device comprising a stack of multiwell plates which is useful in processing such assays.
Multiwell test plates used for isotopic and non-isotopic in-vitro assays are well known in the art and are exemplified, for example, by those described in U.S. Pat. Nos. 3,111,489; 3,540,856; 3,540,857; 3,540,858; 4,304,865; 4,948,442; and 5,047,215. Typically, such test plates have been standardized in the form of the so-called micro-titre plate that provides, in one example, 96 depressions or cylindrical wells of about 0.66 cm in diameter and 1.3 cm deep, arranged in a 12xc3x978 regular rectangular array spaced about 0.9 cm center-to-center.
Selected wells in such a test-plate are used to incubate respective microcultures, followed by further processing to harvest the incubated material. Each well typically includes a filtration element so that, upon application of a vacuum to one side of the plate, fluid in each well is expressed through the filter leaving solids, such as bacteria, debris and the like, entrapped in the well. In typical use, specimens from up to 96 different individuals may be respectively inserted in corresponding wells in the multiwell plate in the course of an assay, the specimens typically all being inserted prior to filtration and completion of the assay.
Oftentimes, it is necessary to transfer biological/chemical samples from one multiwell test plate to another multiwell test plate. The conventional approach to transferring samples is to pipette the samples from the first test plate to the second test plate. However, this approach can be time consuming and difficult depending upon the plate configurations between which samples are being transferred. For example, micro-titre plates providing 384 or 864 cylindrical wells arranged in a regular rectangular array have recently become available. Since each well of a 96-well plate can hold 400 xcexcl or more of sample, while a well of a 384-well plate can only hold, for example, 100 xcexcl of sample, it is conventionally necessary to pipette sample from each well of the 96-well plate to four different wells of the 384-well plate. Obviously, this procedure can be tedious.
With the availability of the new multiwell plates, various assay processing enhancements are desirable. In particular, enhancements in the transfer process are needed for moving samples from, for example, a 96-well plate to a 384- or 864-well plate. The present invention is directed to providing these processing enhancements for the transfer of samples between different multiwell plates.
Briefly summarized, this invention comprises in a first aspect a device for processing biological, biochemical or chemical samples comprising a first multiwell plate and a second multiwell plate. The first multiwell plate has x wells arranged in a regular array, each well of the x wells being capable of receiving a separate sample, and wherein each well of the x wells has an outlet at a lower surface of the first multiwell plate. The second multiwell plate has y wells arranged in a regular array, each well of the y wells being capable of receiving a separate sample, and wherein yxe2x89xa7x. The outlets at the lower surface of the first multiwell plate are arrayed to register with corresponding inlets of xxe2x80x2 wells of the y wells of the second multiwell plate when the first multiwell plate is stacked atop the second multiwell plate, wherein x=x. A means for aligning the first multiwell plate to the second multiwell plate is also provided so that the x wells of the first multiwell plate automatically align to the xxe2x80x2 wells of the second multiwell plate when the first multiwell plate is stacked atop the second multiwell plate using the alignment means. Samples can be directly transferred from the x wells of the first multiwell plate to the xxe2x80x2 wells of the second multiwell plate. As an enhanced aspect, the means for aligning may comprise alignment indicia disposed on the first multiwell plate and corresponding alignment indicia on the second multiwell plate, and/or an alignment guide coupled to either the first multiwell plate or the second multiwell plate so that the x wells of the first multiwell plate automatically align to the xxe2x80x2 wells of the second multiwell plate when the plates are stacked using the alignment indicia and/or guide.
In another aspect, the invention comprises a device for processing biological/chemical samples which includes a first multiwell plate and a second multiwell plate. The first multiwell plate has x wells arranged in a regular array, each well of the x wells being capable of receiving a separate sample, and the second multiwell plate has y wells arranged in a regular array, each well of the y wells also being capable of receiving a separate sample. The device further includes transfer indicia for tracking transfer of sample from the first multiwell plate to the second multiwell plate. The transfer indicia, initially disposed within the x wells of the first multiwell plate, may comprise an inert color indicia which automatically transfers to the second multiwell plate upon transfer of samples from the x wells of said first multiwell plate to wells of said second multiwell plate.
In another aspect, the invention comprises a method for processing biological, biochemical or chemical samples comprising: providing a first multiwell plate having x wells arranged in a regular array, each well of the x wells being capable of receiving a separate sample; providing a second multiwell plate having y wells arranged in a regular array, each well of the y wells being capable of receiving a separate sample; providing transfer indicia within at least one well having sample therein of the x wells of the first multiwell plate; and transferring sample from the first multiwell plate to the second multiwell plate, the transferring including transferring the transfer indicia from the at least one well of the first multiwell plate to at least one well of the second multiwell plate, wherein the transfer indicia tracks transfer of sample from the at least one well of the first multiwell plate to the at least one well of the second multiwell plate for monitoring possible cross-contamination of wells of the second multiwell plate.
To restate, various techniques are provided herein for directly transferring samples from a first well plate having a first number of wells to a second well plate having a second number of wells, wherein the second number of wells is equal to or greater than the first number of wells. Preferably, the second number of wells is a multiple of the first number of wells. As a specific example discussed herein, the first well plate may comprise a 96-well plate and the second well plate a 384-well plate. Significant time and processing complexity is saved by being able to directly transfer between two different multiwell plates. For example, pipetting apparatus is unnecessary to accomplish the transfer.
In addition to direct transfer of samples between well plates, a technique is provided herein to prevent cross-contamination between wells of the receiving plate, as well as to prevent drying of open wells within the receiving plate. In accordance with the principles of this invention, the first well plate may comprise a filter plate so that simultaneous transfer and filtering of samples occurs during the movement of samples from the first well plate to the second well plate. Further, the second well plate can comprise a chromatographic media so that purification of the sample can also simultaneously occur with transfer of the sample from the first well plate into (and through) the second well plate. In accordance with the principles of this invention, a greater volume of sample in the first well plate than can be accommodated in the second well plate can be simultaneously filtered in the first well plate, transferred from the first well plate to the second well plate and purified in the second well plate, before being discharged. Various further advantages, enhancements and examples of processings in accordance with this invention are described further herein.
For example, an alignment mechanism comprising alignment indicia and/or an alignment guide can be provided on either or both of the first multiwell plate and the second multiwell plate. The alignment indicia may comprise positional indicia such as matching color indicia at appropriate corners of the first multiwell plate and the second multiwell plate to facilitate alignment of the outlets of the first multiwell plate to a desired subset of wells of the second multiwell plate. Alternatively, the entire first multiwell plate could be color coded to match color coding on the second multiwell plate to facilitate alignment of the outlets of the first multiwell plate to the desired subset of wells of the second multiwell plate.
Advantageously, the invention also contemplates the use of inert transfer indicia, such as inert color indicia, within the wells for tracking transfer of sample from the wells of the first multiwell plate to the wells of the second multiwell plate. This transfer indicia can confirm proper transfer of samples from the x wells of the first multiwell plate to corresponding wells of the second multiwell plate, as well as indicate whether cross-contamination of samples has occurred between wells of the second multiwell plate. For example, different 96-well plates may have different colored transfer indicia which should be transferred with the samples thereof into a corresponding subset of wells of a 384 well plate. Cross-contamination is thus visually identifiable by verifying accuracy of the colors within the wells of the 384 well plate.